儿童1型糖尿病合并普通变异型免疫缺陷综合征并携带信号转导与转录激活因子3基因新突变一例并文献复习

A boy with type 1 diabetes mellitus combined with common variable immunodeficiency syndrome and signal transducer and activator of transcription 3 gene novel mutation：case report and literature review

目的探讨1例儿童1型糖尿病合并普通变异型免疫缺陷综合征（CVID）致病基因并复习相关文献。方法分析2015年7月我院收治的1例1型糖尿病合并CVID的儿童患者的临床特点并抽提相关家系成员的基因组DNA，全外显子组测序并用Sanger测序验证。结果该患者基因检测证实信号转导与转录激活因子3（STAT3）基因存在杂合错义新生突变c.1073T〉C, P.Leu358Ser，该突变位于“DNA结合域”中，经SIFT、PloyPhen等功能软件预测，该变异可能影响STAT3蛋白结构域功能。结论本患者可能为第1例中国儿童1型糖尿病合并CVID患者，且携带STAT3基因新生突变，拓宽了STAT3基因突变的表型谱。

Objective To identify the features and its pathogenic mechanism in a boy with type 1 diabetes mellitus combined with common variant immunodeficiency syndrome （CVID）. Methods A 9 year old boy with type 1 diabetes was identified with CVID during hospitalization. The clinical features was analyzed. Genomic DNA was extracted, followed by amplification with polymerase chain reaction, whole？exome sequencing （WES） and then Sanger sequencing in his family members. Results A novel heterozygous missense mutation c.1073T〉C, P.Leu358Ser of signal transducer and activator of transcription 3 （STAT3） gene was confirmed by genetic testing, this mutation was located in the＂DNA binding domain＂, which might affect the functional domains of STAT3 protein predicted by SIFT, PloyPhen and other software. Conclusion The patient may be the first case of Chinese children with type 1 diabetes mellitus combined with CVID and carrying the STAT3 gene novel mutation after retrieving the existing database, which expands the phenotypic spectrum of STAT3 gene mutations.